The Reproductive Pathobiology Group has focused its research on defining the pathogenesis/carcinogenesis of disorders affecting the reproductive tract of humans and rodents, and assessing the role of environmental and endogenous factors in the induction of these disorders.Our group has used archival mouse and human tissues to determine the presence of growth factors (e.g., TGF-a, TGF-b1, IGF-I, EGF) in uterine leiomyomas ("fibroids") and leiomyosarcomas in rodents and humans. Data from our studies show that TGF-a (mature form) is expressed exclusively in malignant uterine smooth muscle cell tumors (leiomyosarcomas) of mice. However, in benign uterine smooth muscle cell tumors (leiomyomas) of mice and humans this growth factor is not present. We have also found a positive correlation between TGF-a staining and cell proliferation as measured by the expression of proliferating cell nuclear antigen (PCNA) in the malignant uterine leiomyosarcomas, and that immunoexpression of epidermal growth factor receptor (receptor for TGF-a) is increased in leiomyosarcomas compared to the benign uterine leiomyomas. Studies to assess the immunoexpression of factors (Bcl-2; Bax) possibly modulating cell survival and death in human uterine leiomyomas are underway.